Article

Effects of Extinction on Classical Conditioning and Conditioning-Specific Reflex Modification of Rabbit Heart Rate

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Abstract

Understanding the mechanisms of fear extinction has become increasingly important for treating a number of disorders, particularly post-traumatic stress disorder. Conditioning of rabbit heart rate (HR) is an established model for studying fear, yet little is known about procedures for extinguishing it other than repeated presentations of cue(s) associated with the fear-inducing event. The following study examined the effects of conditioned stimulus (CS) alone, unconditioned stimulus (US) alone, unpaired CS/US presentations, continued CS-US pairings, or no further stimulation on rabbit HR following HR conditioning. We have previously shown the rabbit HR response to the US can change as a function of learning when measured in the absence of the CS, a phenomenon referred to as conditioning-specific reflex modification (CRM). More specifically, the HR exhibits a deceleration in response to the US reminiscent of the conditioned bradycardia that develops to the CS. Consequently, the following study also examined the effects of extinction treatments on HR CRM. For HR conditioned responses (CRs), CS-alone and unpaired CS/US presentations were the most successful extinction treatments. For HR CRM, all conditions led to a reduction in CRM except for a subset of rabbits that maintained high levels following unpaired extinction, indicating a dissociation between extinction of HR CRs and CRM. The findings highlight the parameters of HR extinction, the transient nature of HR CRM, vagal involvement in both acquisition and extinction of HR CRM, and suggest that HR CRM cannot be fully explained as a CR that has generalized from the CS to the US.

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... Thus, rabbits were assigned to groups that received pretesting, conditioning and post testing with ES near the eye (n=8), to the back (n=9), testing with ES near the eye and conditioning with ES to the back (n=9) or testing with ES to the back and conditioning with ES near the eye (n=9). The group with ES to the eye during training and testing served as our standard HR conditioning and HR CRM group (Burhans et al., 2008; Burhans et al., 2010;), and the group with ES to the back during training and testing tested whether HR conditioning and HR CRM could be detected when ES was applied to the back. Groups trained in one location (eye or back) and tested in the other location (back or eye) determined whether HR CRM could generalize between locations. ...
... Stimulus onset occurred 2,200 ms after trial onset providing a total post-stimulus observation interval of 3,800 ms. Details for detection of heartbeats and components of the ECG signal have been described in detail elsewhere (Burhans et al., 2010; ). Briefly, heartbeats were detected in the filtered ECG signal with a templatematching algorithm created in LabVIEW software. ...
... Visual inspection of the data corrected any false positives or negatives as a result of artifacts such as those related to movement. Data were expressed as a change in IBI (inverse of heart rate) to the CS or US from the prestimulus baseline and was used because it is consistent with our previously published studies and with much of the rabbit HR conditioning literature (Burhans et al., 2010; McEchron et al., 2003; Powell, Churchwell, & Burriss, 2005; Supple, Jr., Sebastiani, & Kapp, 1993). In addition to changes in IBI, average topographies of the IBIs during US testing and HR conditioning were generated and used as a guide to determine the nature of changes in the IBI as a function of time and the appropriate post-stimulus window for analysis of CRM to the two different USs and CRs to the CS. ...
Article
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Heart rate conditioning is used as an index of conditioned fear and is important for understanding disorders of anxiety and stress, including post traumatic stress disorder (PTSD). One important feature of PTSD is that patients generalize conditioned fear from danger signals to safety signals especially when the two signals have overlapping features. What has not been determined is whether generalization occurs between unconditioned stimuli with overlapping features. In the current experiment, heart rate conditioning and conditioning-specific reflex modification of rabbit heart rate were examined as a function of two different unconditioned stimulus locations. Heart rate conditioning occurred at identical terminal levels whether electrical stimulation was presented near the eye or on the back. Despite different heart rate response topographies to electrical stimulation at the two locations, conditioning-specific reflex modification was detected near the eye and on the back and appeared to generalize between the locations. Interestingly, only conditioning-specific reflex modification detected on the back persisted for a week after heart rate conditioning. This persistence may be a model for some features of post traumatic stress disorder. Overgeneralization of unconditioned responses to unconditioned stimuli similar to the trauma may also be an important aspect of PTSD modeled here.
... These previous studies on HR conditioning in rabbits have mainly focused on the neural mechanisms behind the development of conditioned HR changes to a CS such as an auditory tone that is paired with a US, often shock. However, work in our laboratory has shown that the conditioning procedure can also modify unconditioned HR responses to the US when it is presented in the absence of the CS following conditioning (Burhans, Smith-Bell, & Schreurs, 2008;Burhans, Smith-Bell, & Schreurs, 2010;Schreurs et al., 2007;Schreurs, Crum, Wang, & Smith-Bell, 2005;Schreurs, Smith-Bell, & Burhans, 2011b). These changes are not observed in rabbits receiving explicitly unpaired CS-US presentations and therefore represent a learning-related cardiovascular change in the unconditioned response to the US that we refer to as conditioning-specific reflex modification (CRM). ...
... The observed HR change closely resembles the conditioned bradycardia that develops to the tone CS, suggesting that HR CRM may in part be a generalized conditioned response . However, we have shown that there are certain conditions that can extinguish HR CRM while leaving the HR conditioned response intact, so there is also evidence for a dichotomy between the two types of responding (Burhans et al., 2010). HR CRM has also been shown to generalize across USs with overlapping features and is enhanced, along with HR conditioning, by dietary cholesterol (Schreurs et al., 2007;Schreurs et al., 2011b). ...
... Data were expressed as a change in interbeat interval (Δ IBI) to the CS or US from a pre-stimulus baseline. There is continued debate in the field of neurophysiology about the appropriate measurement of HR change, but we have selected to measure and report on change in IBI since it is consistent with our previously published studies and a good deal of the HR conditioning literature (Burhans et al., 2010;McEchron, Tseng, & Disterhoft, 2003;Powell, Churchwell, & Burriss, 2005;Schreurs et al., 2007;Supple, Jr. & Kapp, 1993). ...
Article
Heart rate (HR) conditioning in rabbits is a widely used model of classical conditioning of autonomic responding that is noted for being similar to the development of conditioned heart rate slowing (bradycardia) in humans. We have shown previously that in addition to HR changes to a tone conditioned stimulus (CS), the HR reflex itself can undergo associative change called conditioning-specific reflex modification (CRM) that manifests when tested in the absence of the CS. Because CRM resembles the conditioned bradycardic response to the CS, we sought to determine if HR conditioning and CRM share a common neural substrate. The central nucleus of the amygdala (CeA) is a critical part of the pathway through which conditioned bradycardia is established. To test whether the CeA is also involved in the acquisition and/or expression of CRM, we inactivated the CeA with muscimol during HR conditioning or CRM testing. CeA inactivation blocked HR conditioning without completely preventing CRM acquisition or expression. These results suggest that the CeA may therefore only play a modulatory role in CRM. Theories on the biological significance of conditioned bradycardia suggest that it may represent a state of hypervigilance that facilitates the detection of new and changing contingencies in the environment. We relate these ideas to our results and discuss how they may be relevant to the hypersensitivity observed in fear conditioning disorders like post-traumatic stress.
... In the human study, Vervleit and coworkers found that compared to normal extinction, only unpaired extinction prevented renewal of fear responses in people trained to discriminate one of two pictures paired with shock (Vervleit et al., 2010). In rabbit classical conditioning experiments designed to extinguish CRs, comparable extinction of CS responding occurs following CS-alone or unpaired CS/US presentations in the nictitating membrane response (NMR, Schreurs et al., 2000) and heart rate (HR) response (Burhans et al., 2009). However, unpaired presentations were able to extinguish conditioning-specific increases in the unconditioned response (UR) known as conditioningspecific reflex modification (CRM) better than CS-alone presentations (Schreurs et al., 2000). ...
... However, unpaired presentations were able to extinguish conditioning-specific increases in the unconditioned response (UR) known as conditioningspecific reflex modification (CRM) better than CS-alone presentations (Schreurs et al., 2000). CRM is an increase in size and shape of URs that occurs when these responses are measured in the absence of the CS following classical conditioning of the rabbit NMR (Gruart & Yeo, 1995; Schreurs et al., 1995; Schreurs et al., 2000; Buck et al., 2001; Wikgren et al., 2002; Seager et al., 2003; Schreurs et al., 2006; Burhans et al., 2008) and HR ( Burhans et al., 2008; Burhans et al., 2009). The ability of unpaired presentations to diminish both CS responses and exaggerated US responses (i.e., CRM) suggests it may be relevant for treating symptoms of PTSD (Seager et al., 2003; Schreurs et al., 2006; Burhans et al., 2008). ...
... To determine if unpaired extinction could be made more clinically relevant, we classically conditioned the rabbit NMR and reduced US intensity and duration of unpaired extinction. We wanted to know if a weaker US or fewer days of extinction would be effective in extinguishing both CRs and CRM (Schreurs et al., 1995; Schreurs et al., 2000; Buck et al., 2001; Seager et al., 2003; Burhans et al., 2009). Given the heightened physiological indices found in patients with PTSD including HR (Pitman et al., 2006), we measured HR during testing as a physiological measure of rabbits' emotional reactivity to the US. ...
Article
Extinction of fear is important for treating stress-related conditions particularly post-traumatic stress disorder (PTSD). Although traditional extinction presents the feared stimulus by itself, there is evidence from both clinical and basic research that repeatedly presenting the feared stimulus by itself does not prevent fear from returning. This renewal or relapse can be "thwarted" by unpaired extinction-presentations of the feared stimulus and the event producing the fear. However, no matter how effective standard unpaired extinction may be in the laboratory, repeated presentation of a traumatic event is untenable. To make an unpaired extinction procedure more clinically relevant, we classically conditioned the rabbit nictitating membrane response using electrical stimulation or air puff as the unconditioned stimulus and then during unpaired extinction reduced both the intensity of the unconditioned stimulus and the days of unpaired stimulus presentations. We found unpaired extinction reduced conditioned and exaggerated unconditioned responding (an animal analog of PTSD called conditioning-specific reflex modification) and could be accomplished with a weak unconditioned stimulus as long as extended presentations were used. Surprisingly, brief presentations of a weak unconditioned stimulus or extended presentations of a strong one made the exaggerated responses stronger. One implication is that brief treatment may not just be ineffectual; it may heighten the symptoms of PTSD. Another implication is that using strong stimuli may also heighten those symptoms.
... CRM is a function of conditioning parameters such as number of conditioned stimulus (CS)-US pairings and US intensity, and it can generalize from one US to another and from one anatomical location to another (Buck et al., 2001;Schreurs et al., 1995;Schreurs et al., 2000;Seager et al., 2003). CRM is also sensitive to context, undergoes extinction, incubation, and spontaneous recovery, is susceptible to drugs and dietary manipulations, and has potential as a model for developing PTSD treatment (Burhans et al., 2010;Schreurs et al., 2005;Schreurs et al., 2006;Schreurs et al., 2007;Schreurs et al., 2011a;Schreurs et al., 2011b;Schreurs et al., 2011c). Conditioning-specific changes in responding to the US characteristic of CRM have been described by several groups in rabbits (Gruart & Yeo, 1995;Schreurs et al., 1995;Wikgren & Korhonen, 2001) and in rats (Servatius et al., 2001). ...
... We have previously noted the topography of a UR after CS-US pairings bears a striking resemblance to the CR-UR sequence that occurs during CS-US pairings, not only for the NMR (Schreurs et al., 2000) but for heart rate as well (Burhans et al., 2010;Schreurs et al., 2005;Schreurs et al., 2011a). That is not to say that CRM is simply a CR elicited by weak shocks after training because extinguishing CRs does not extinguish CRM and extinguishing CRM does not extinguish CRs (Schreurs et al., 2000). ...
Article
Animal models of posttraumatic stress disorder (PTSD) are based on fear conditioning where innocuous cues elicit reactions that originally occur to traumatic events-a core feature of PTSD. Another core feature is hyperarousal-exaggerated reactions to stressful events. One limitation of animal models of PTSD is that group effects do not model the sporadic incidence of PTSD. We developed an animal model of PTSD in which rabbit nictitating membrane responses become exaggerated as a function of classical conditioning to a tone conditioned stimulus (CS) paired with a shock unconditioned stimulus (US). Exaggerated responses to the US are a form of hyperarousal termed conditioning-specific reflex modification (CRM) and occur in the absence of the CS. Inspecting data across several experiments, we determined 25% of our rabbits exhibit strong CRM despite all subjects having high levels of conditioning. To determine how prone rabbits were to CRM (susceptibility) or how resistant (resilience), we examined data from 135 rabbits analyzing for factors during CS-US pairings and during US prescreening that would predict CRM. We found the magnitude of CRM was correlated with the onset latency and area of conditioned responding during CS-US pairings and with the peak latency of a response during US pretesting. In an animal model of PTSD that more accurately reflects clinical prevalence, we can begin to predict susceptibility not only during responding to a stressful conditioning situation but also during a screening process before the stressful situation takes place. The results suggest relatively innocuous testing may help detect PTSD after trauma and screen for it before trauma occurs. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
... In contrast, the changes within this response pattern might be different in aversive compared to appetitive conditioning. In studies investigating aversive conditioning of cardiac responses, a stronger deceleration following the CS+ compared to the CS− is typically observed in a certain time window after CS onset (2-6 s after CS onset for humans) in human (Bradley et al., 2005;De Leon, 1964;Hugdahl, 1979;López et al., 2009;Panitz et al., 2018;Sperl et al., 2016; but also see Hodes et al., 1985) and non-human subjects (Applegate et al., 1982;Burhans et al., 2010;Holdstock & Schwartzbaum, 1965;Kuniecki et al., 2002;Pascoe & Kapp, 1985). Since this deceleration is reliably observed towards fear-eliciting stimuli, it is often termed "fear bradycardia" De Leon, 1964;Hugdahl, 1979;López et al., 2009). ...
Article
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While the examination of conditioned cardiac responses is well established in human fear conditioning research, comparable studies using less-aversive or rather appetitive unconditioned stimuli (UCS) are sparse and results are mixed. Therefore, the aim of this study was a systematic analysis of cardiac reactions in aversive and appetitive conditioning. Olfactory stimuli were used as unconditioned stimuli as they are suitable reinforcers in both an aversive and an appetitive conditioning offering the opportunity for a comparison between conditioned responses. In total, n = 86 participants took part in both an aversive and an appetitive differential conditioning task with a counterbalanced order across participants. Aversive or appetitive odors, respectively, served as UCS and neutral geometrical figures as CS. Subjective ratings, skin conductance response (SCRs), and evoked cardiac reactions were analyzed and compared between tasks. Conditioned responses in subjective ratings could be observed in both aversive conditioning and appetitive conditioning, while SCRs discriminated between CS+ and CS− in aversive conditioning only. Regarding conditioned cardiac responses, the deceleration for the CS+ was longer than for the CS− in both tasks. In addition, a higher deceleration magnitude and a shorter acceleration for the CS+ as compared to the CS− were found in aversive but not in appetitive conditioning. There were medium-size correlations between aversive and appetitive CRs for subjective ratings and none for physiological responses. The results suggest similarities between cardiac response patterns in aversive and appetitive conditioning, which implies that bradycardia in conditioning might not be fear-specific but presents a valence-independent CS-elicited bradycardia.
... This response is controlled by the PNS, which influences HR very quickly due to the action of acetylcholine on the heart's sinoatrial node, leading to rapid initial bradycardia (Berntson et al., 1997;Pumprla et al., 2002). Studies with healthy subjects have demonstrated that fear bradycardia can be conditioned in response to threatening stimuli (Castegnetti et al., 2016) and animal studies have shown that it can be extinguished (Burhans et al., 2010). Further, we recently found that fear extinction in rodents was associated with a reduction of conditioned bradycardia (Swiercz et al., 2018). ...
Article
Background Trauma and symptoms of posttraumatic stress disorder (PTSD) have repeatedly been linked to impaired cardiovascular functioning. Poor fear extinction is a well-established biomarker of PTSD that may provide insight into mechanisms underlying cardiovascular risk. The current study probed the cardiovascular response to extinction in a sample of trauma-exposed individuals. Methods Participants were 51 trauma-exposed women who underwent a fear conditioning paradigm. Heart rate (HR) during extinction was examined in response to a conditioned stimulus that was previously paired with an aversive unconditioned stimulus (CS+) and one that was never paired (CS-). Heart rate variability (HRV) was calculated at baseline and during the extinction session. Results Consistent with fear bradycardia, initial HR deceleration (.5-2s) after CS + onset occurred during early extinction and appeared to extinguish over time. Higher baseline HRV was significantly associated with greater fear bradycardia during early extinction. Conclusions This is the first study to demonstrate a pattern of fear bradycardia in early extinction, which was associated with higher HRV levels and decreased over the course of the extinction phase. These results suggest that increased fear bradycardia may be indicative of greater vagal control (i.e., HRV), both of which are psychophysiological biomarkers that may influence cardiovascular and autonomic disease risk in trauma-exposed individuals.
... CRM is a function of conditioning parameters particularly the number of CS-US pairings (Schreurs et al., 1995) and US intensity (Seager et al., 2003), and can generalize from one US to another (Buck et al., 2001) and from one site of US application to another (Schreurs, Smith-Bell, & Burhans, 2011c). CRM is also sensitive to context (Schreurs, Gonzalez-Joekes, & Smith-Bell, 2006), undergoes extinction (Schreurs et al., 2000;Schreurs, Smith-Bell, & Burhans, 2011b;Burhans, Smith-Bell, & Schreurs, 2015), incubation (Schreurs, Smith-Bell, & Burhans, 2011a), and spontaneous recovery, can occur in both skeletal and autonomic response systems (Schreurs, Crum, Wang, & Smith-Bell, 2005;Burhans, Smith-Bell, & Schreurs, 2010;Schreurs et al., 2011c), and is susceptible to drugs (Wang, Darwish, & Schreurs, 2006; and dietary manipulations (Schreurs, Smith-Bell, Darwish, Stankovic, & Sparks, 2007). CRM has been reported in rabbits by a number of other laboratories (Gruart and Yeo, 1995;Wikgren and Korhonen, 2001) and can also be observed in rats (Servatius, Brennan, Beck, Beldowicz, & Coyle-DiNorcia, 2001). ...
Article
We have developed a rabbit model of posttraumatic stress disorder (PTSD) which recapitulates several core features of PTSD, particularly hyperarousal and conditioned responding to trauma-associated cues. The work conducted with this model has all been done in male rabbits and given sex differences in PTSD prevalence, it is important to expand our animal model of PTSD to include female rabbits to determine if they develop core features of PTSD, and if those core features can be treated. This is particularly important because, contrary to human studies, nearly all animal studies have found that males are consistently more vulnerable to various forms of acute and chronic stress than females. Using eyeblink conditioning in which we paired tone with a brief periorbital shock, we found that although both male and female rabbits acquired identical levels of conditioning, females showed more hyperarousal after conditioning but seemed to respond somewhat better to treatment.
... In laboratory animals, it has been shown that frequent contact increases compliance stress tolerance and reduces fear response. 9,10 When rabbits are healthy, rabbit owners should be encouraged to handle their pet whenever possible. Nevertheless, minimizing handling and stressors in the environment should be a constant goal of exotic clinicians, especially with rabbits that are not used to being handled. ...
Article
Rabbits have the ability to hide their signs and often present in a state of decompensatory shock. Handling can increase susceptibility to stress-induced cardiomyopathy and specific hemodynamic changes. Careful monitoring with a specific reference range is important to detect early decompensation, change the therapeutic plan in a timely manner, and assess prognostic indicators. Fluid requirements are higher in rabbits than in other small domestic mammals and can be corrected both enterally and parenterally. Critical care in rabbits can be extrapolated to many hindgut fermenters, but a specific reference range and dosage regimen need to be determined.
... Extensive research on the rabbit nictitating membrane response (NMR) has shown that the NMR reflex, once thought to be invariant and automatic, can become enhanced after classical NMR conditioning (Schreurs, 2003;Burhans et al., 2010). This learning-related change is observed in the absence of the conditioned stimulus (CS) and is referred to as conditioning-specific reflex modification (CRM). ...
Article
Extensive research on the rabbit nictitating membrane response (NMR) has shown that the NMR reflex can become exaggerated following classical fear conditioning. This learning-related change is referred to as conditioning-specific reflex modification (CRM) and is observed in the absence of the conditioned stimulus. The aim of the current study was to examine the sensitivity of the CRM paradigm to serotonergic manipulation with fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor for anxiety disorders. To assess the effect of fluoxetine on exaggerated reflexive responding indicative of CRM and on conditioned cued fear, rabbits underwent delay NMR conditioning (pairings of tone and periorbital shock) and were tested for CRM, followed by 5 days of daily fluoxetine (0.03, 0.3, or 3.0 mg/kg) or saline injections. CRM was reassessed 1 day and 1 week later, followed by a retention test of conditioned responses (CRs) to the tone. Fluoxetine (3.0 mg/kg) enhanced CRM and retention of conditioned responses, a week after treatment ceased, and this is in agreement with the reports on increased anxiety-like behaviors in other animal models and humans. The CRM paradigm, therefore, may provide important insight into the mechanisms underlying the paradoxical selective serotonin reuptake inhibitor effects.
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To further understand mechanisms of neuropsychiatric disease(s) and their impact on physiological systems, improved pre-clinical models and innovative methodology are needed to assess the internal physiological state of the animal in real-time. To address this challenge we developed a customizable software-based program for Ponemah࣪ that takes into account the animals diurnal and resting cardiovascular state in a home-cage environment. Using an integrated Pavlovian fear conditioning and cardiovascular telemetry approach in mice, we demonstrate for the first time a novel software add-on application that can remotely trigger a conditioned stimulus (CS) (i.e., audible tone) based on the animals instantaneous cardiovascular state while in its home-cage environment. This new cardiovascular behavioral experimental tool extends the ability to quantify integrated physiological correlates of learned fear and may aid in further understanding mechanisms related to enhanced cardiovascular and autonomic arousal in fear and anxiety based disorders.
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Averaging behavioral data such as the nictitating membrane response (NMR) across subjects can conceal important individual and group differences. Analyses were conducted of NMR data from rabbits that were grouped based on the point during NMR conditioning when subjects produced 8 conditioned responses (CR) in a set of 10 trials. This resulted in five groups (Early Day 1, Late Day 1, Early Day 2, Late Day 2, Early Day 3) in which group differences in CR acquisition rates were found. Percent (%) CRs were not found to increase monotonically and between-session differences in% CR were found. Conditioning-specific reflex modification (CRM) of the NMR is a type of enhanced reflexive responding of the NMR that is detected when the unconditioned stimulus (US) is presented in the absence of the conditioned stimulus (CS) following paired classical conditioning. CRM occurred in some subjects in all five groups. Subjects from both the group that was fastest and the group that was slowest to reach the learning criterion had unconditioned response (UR) topographies following NMR conditioning that strongly resembled the CR-UR response sequence elicited during NMR conditioning. This finding was most pronounced when the US duration used to assess CRM was equivalent to that used during NMR conditioning, further evidence to support the hypothesis that CRM is a CR that has generalized from the CS to the US. While grouping data based on conditioning criteria did not facilitate identifying individuals more predisposed to exhibiting CRM, strong CRM only occurred in the groups that reached the conditioning criterion the fastest.
Chapter
PTSD is a major health problem for military and civilian populations and treatment has proven to be less than effective. There are many people exposed to trauma who suffer flashbacks, bad dreams, emotional numbing, fear, anxiety, sleeplessness, hypervigilance, hyperarousal, and an inability to cope. Current behavioral and drug treatment strategies for PTSD are based on animal models of fear conditioning which typically do not focus on treating all PTSD symptoms. For example, the extinction of fear to trauma-associated trigger cues using techniques such as cognitive behavioral therapy does not deal with the general hyperarousal experienced by people with PTSD. A new animal model based on classical conditioning of the rabbit has been developed in which conditioning and hyperarousal can both be extinguished using modified unpaired stimulus presentations. This potential form of treatment might be implemented in clinical practice using a virtual reality environment.
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The individual typological features of conditioned reflex fear were studied in groups of active and passive rabbits selected on the basis of analysis of their behavior in the open field and dark-light boxes by developing a classical conditioned reflex using a combination of a light (4 sec) and electrocutaneous stimulation of the hindpaws (10 Hz, 0.5 sec). Changes in respiratory and heart rates in the animals in response to stimulus combinations during training were analyzed. Conditioned defensive responses to light (freezing) were associated with reductions in respiratory and heart rates occurring in response to the light, i.e., before electrocutaneous stimulation. Active rabbits contrasted with passive rabbits in showing greater motor reactions, higher heart rates, delayed onset of conditioned reflex respiratory slowing to a later stage of training, and the absence of persistent bradycardia. Thus, judging from the these few autonomic measures, active animals experienced lower levels of fear than passive animals. The active and passive behavioral strategies persisted after training.
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Although the conditioned cardiac fear response is an important index of psychophysiological fear processing, underlying neural mechanisms remain unclear. N = 22 participants underwent differential fear conditioning and extinction with face pictures as conditioned stimuli (CS) and loud noise bursts as aversive unconditioned stimulus (US) on Day 1 and a recall test 1 day later. We assessed ERPs, evoked heart period (HP), and time-lagged within-subject correlations of single-trial EEG amplitude and HP as index for corticocardiac coupling in response to the CS. Fear-conditioned stimuli (CS+) triggered cardiac deceleration during fear acquisition and recall. Meanwhile, only during Day 1 acquisition, CS+ evoked larger late positivities in the ERP than CS-. Most importantly, during Day 2 recall, stimulus-evoked single-trial EEG responses in the time window between 250 and 500 ms predicted the magnitude of cardiac fear responses 2 to 5 s later. This marker of corticocardiac coupling selectively emerged in response to not previously extinguished CS+ but was absent in response to CS- or previously extinguished CS+. The present results provide first evidence that fear conditioning and extinction modulate functional corticocardiac coupling in humans. Underlying mechanisms may involve subcortical structures enhancing corticocardiac transmission to facilitate processing of consolidated conditioned fear. © 2015 Society for Psychophysiological Research.
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Conditioning-specific reflex modification (CRM) of the rabbit's nictitating membrane response (NMR) describes changes in responding to an unconditioned stimulus (US) when the rabbit is tested in the absence of the conditioned stimulus. Specifically, after at least 3 days of tone-electrical stimulation pairings, responses to the US increase in size, especially at intensities weaker than the training intensity. CRM is similar to classical conditioning in that it is a function of the strength of conditioning, it can be extinguished, and it can be generalized from one stimulus to another. To compare CRM and classical conditioning further, we conducted three experiments to examine the effects of US intensity (1.0, 2.0, and 4.0 mA) on CRM. CRM was weak following conditioning with 1.0 mA and extremely strong following conditioning with 2.0 mA and 4.0 mA. The data suggest that CRM is a function of US intensity and have implications for posttraumatic stress disorder, a disorder potentially modeled by CRM.
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Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder.
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A series of experiments used a within-subject design to study spontaneous recovery of fear responses (freezing) to an extinguished conditioned stimulus (CS) in rats. Experiments 1, 2, 3, and 4 demonstrated that: a remotely extinguished CS elicited more freezing than a recently extinguished one on a common test; that the CS showing recovery underwent greater response loss across additional extinction than the one lacking recovery; and that spontaneous recovery and deepening of response loss survived reconditioning. Experiment 5 demonstrated that an excitor extinguished in compound with a CS showing recovery suffered greater loss than an excitor extinguished in compound with a CS not showing recovery, implying that the differential change is regulated by a common error term. Experiments 6 and 7 demonstrated that extinction of a compound composed of two CSs, one showing recovery and a second lacking recovery, produced greater loss to the CS that showed recovery, implying that the change is also regulated by individual error term.
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The effects of combat-related posttraumatic stress disorder (PTSD) on heart rate (HR) responding associated with a discriminative delay eyeblink (EB) conditioning paradigm are reported. Combat PTSD+, Combat PTSD-, and Noncombat PTSD- veterans were assessed with psychometric self-report measures, and baseline heart rate variability (HRV) was measured before receiving a 72-trial session of discriminative EB classical conditioning. Two types (red or green light) of conditioned stimuli (CS) were used: one (CS+) predicted a tone, followed immediately by an aversive stimulus (corneal airpuff); the other (CS-) predicted a tone alone, not followed by the airpuff. The light signal was presented for 5 seconds, during which HR was measured. On all psychometric measures, the PTSD+ subgroup was significantly different from the PTSD- subgroups (Combat + Noncombat), and the PTSD- subgroups did not significantly differ from each other. A linear deceleration in HR to CS+ and CS- signals was found in the combined PTSD- subgroup and on CS- trials in the PTSD+ subgroup, but was not present on CS+ trials in the PTSD+ subgroup. Results are interpreted with respect to a behavioral stages model of conditioned bradycardia and in terms of neural substrates which are both critical to HR conditioning and known to be abnormal in PTSD.
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The effects of lesions of the cerebellum on the acquisition and retention of aversive Pavlovian conditioned bradycardia were examined in rabbits. Lesions of the anterior cerebellar vermis severely attenuated the acquisition of simple conditioned bradycardia without disrupting baseline heart rate (HR), or unconditioned HR responses. Also, lesions of the vermis performed after the acquisition of conditioned bradycardia eliminated evidence of prior conditioning. Bilateral lesions of the cerebellar hemispheres did not affect conditioned or unconditioned HR responses. These results were interpreted to indicate that anterior vermis lesions specifically disrupted part of an essential conditioned response pathway without interfering with the neural circuits that mediate unconditioned HR responding. These lesion data, coupled with recent electrophysiological evidence of learning-related changes in neuronal activity within the anterior vermis of the fear-conditioned rabbit, suggest that the anterior cerebellar vermis is critically involved in the acquisition and retention of this rapidly learned autonomic conditioned response.
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We made intradendritic recordings in Purkinje cells (n = 164) from parasaggital slices of cerebellar lobule HVI obtained from rabbits given paired presentations of tone and periorbital electrical stimulation (classical conditioning, n = 27) or explicitly unpaired presentations of tone and periorbital stimulation (control, n = 16). Purkinje cell dendritic membrane excitability, assessed by the current required to elicit local dendritic calcium spikes, increased significantly in slices from animals that received classical conditioning. In contrast, membrane potential, input resistance, and amplitude of somatic and dendritic spikes were not different in slices from animals given paired or explicitly unpaired stimulus presentations. The location of cells with low thresholds for local dendritic calcium spikes suggested that there are specific sites for learning-related changes within lobule HVI. These areas may correspond to learning "microzones" and are consistent with locations of learning-related in vivo changes in Purkinje cell activity. Application of 4-aminopyridine, an antagonist of the rapidly inactivating potassium current IA, reduced the threshold for dendritic spikes in slices from naive animals to levels found in slices from trained animals. In cells where thresholds for eliciting parallel fiber-stimulated Purkinje cell excitatory postsynaptic potentials (EPSPs) were measured, levels of parallel fiber stimulation required to elicit a 6-mV EPSP as well as a 4-mV EPSP (n = 30) and a Purkinje cell spike (n = 56) were found to be significantly lower in slices from paired animals than unpaired controls. A classical conditioning procedure was simulated in slices of lobule HVI by pairing a brief, high-frequency train of parallel fiber stimulation (8 pulses, 100 Hz) with a brief, lower frequency train of climbing fiber stimulation (3 pulses, 20 Hz) to the same Purkinje cell. Following paired stimulation of the parallel and climbing fibers, Purkinje cell EPSPs underwent a long-term (> 20 min) reduction in peak amplitude (-24%) in cells (n = 12) from animals given unpaired stimulus presentations but to a far less extent (-9%) in cells (n = 20) from animals given in vivo paired training. Whereas 92% of cells from unpaired animals showed pairing-specific depression, 50% of cells from paired animals showed no depression and in several cases showed potentiation. Our data establish that there are localized learning-specific changes in membrane and synaptic excitability of Purkinje cells in rabbit lobule HVI that can be detected in slices 24 h after classical conditioning. Long-term changes within Purkinje cells that effect this enhanced excitability may occlude pairing-specific long-term depression.
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The involvement of the cerebellar vermis in the control of affective behaviors and in the coordination of fear-related somatic and autonomic conditioned responses is reviewed in this paper. In particular, the review focuses on the role of the midline cerebellum (vermis) on the acquisition and/or expression of classically conditioned bradycardia in the rabbit. The results of both lesioning and electrophysiological experiments indicate that the cortex of lobule III through VII is important, although not essential, in the acquisition and retention of this response, but it is not the site of its memory trace. The time course of the development of the conditioned bradycardia in neonatal rabbits is also described. The results obtained are consistent with the possibility that the expression of conditioned bradycardia may depend on the complete maturation of cerebellum. Moreover, preliminary data on the effects of the ablation of cerebellar vermis, performed at early stages of development, on the characteristics of conditioned bradycardia showed by adult rabbits are presented. These results indicate that cerebellar vermis is essential for the correct maturation of the response and that the timing of the lesion is critical for determining the characteristics of conditioned bradycardia in the adult.
Article
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Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus (US) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit nictitating (Oryctolagus cuniculus) membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or US manipulation. CRM occurred after 12 days of CS-US pairings but not following unpaired CS/US presentations or restraint. CRM survived CS-alone and CS/US-unpaired extinction of the conditioned response (CR) but not presentations of the US alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning.
Chapter
To achieve a more complete understanding of the neural substrates of learning and memory, several goals must be attained. Clearly, identifying critical brain areas that participate in the acquisition, storage, and retrieval of information would be necessary. Having identified these areas, it would then be necessary to determine the exact manner in which each contributes to learning and memory processes. This chapter reviews selected examples of the current research efforts of neuroscientists who use vertebrate models to investigate the neural substrates of associative learning and memory in the intact, behaving animal. Our discussion emphasizes research that incorporates the integrated use of a variety of methods and research strategies and begins with a discussion of the desirable characteristics of a vertebrate model with which to study the neural substrates of learning and memory. The chapter focuses primarily on a discussion of nonspecific CRs, although two models featuring specific CRs are described in a later section. A discussion of interactions between specific and nonspecific CRs is included at the end of the chapter.
Article
Classical conditioning of the rabbit's nictitating membrane (NM) response usually requires several dozen trials for the first conditioned response (CR) to appear. However, as the number of trials is reduced to one per session, the rate of acquisition increases progressively, and the first CR appears in less than a dozen trials. This large and systematic variation in the rate of conditioning challenges recent conclusions by Lennartz and Weinberger (1992). They use the rabbit NM preparation as an example of a slow-conditioning, 'specific' system that is distinct from a fast-conditioning, 'nonspecific' system, such as heart rate.
Chapter
Classical conditioning can be characterized as an experimenter-defined set of operations, involving a temporal contingency between two stimuli, that are independent of the subject’s behavior. Viewed from this perspective, classical conditioning is unique among the various approaches to the study of behavior because it allows for a level of experimental control that is rarely encountered in the behavioral sciences. Furthermore, if the experimenter chooses the appropriate stimulus parameters, an analysis of the temporal relationships among the responses elicited and the stimuli used permit the externalization of otherwise internal events that may not be directly observed. The information gleaned from this type of analysis can be used to study the adaptive functions of learned associations (Hollis, 1984; Shettleworth, 1983; Culler, 1938; Palmerino et al., 1980; Dworkin, 1993) or the processes that underlie the associations formed during learning (Gormezano, 1972; Schneiderman, 1972, 1974; Moore, 1986; Thompson et al., 1983). In recent years, the “internal events” described by (1972) have been investigated directly using electrophysiological techniques to monitor neural activity during conditioning. In addition, modern neuroanatomic tracing techniques have allowed investigators to chart the central nervous system (CNS) pathways that provide the links between the stimuli and responses involved in conditioning (Weinberger & Diamond, 1987; Kapp et al., 1990; Thompson & Steinmetz, 1992; Davis, 1992; McCabe et al, 1992; Powell, 1994; Ledoux, 1995).
Article
The effects of combat-related posttraumatic stress disorder (PTSD) on heart rate (HR) responding associated with a discriminative delay eyeblink (EB) conditioning paradigm are reported. Combat PTSD+, Combat PTSD−, and Noncombat PTSD− veterans were assessed with psychometric self-report measures, and baseline heart rate variability (HRV) was measured before receiving a 72-trial session of discriminative EB classical conditioning. Two types (red or green light) of conditioned stimuli (CS) were used: one (CS+) predicted a tone, followed immediately by an aversive stimulus (corneal airpuff); the other (CS−) predicted a tone alone, not followed by the airpuff. The light signal was presented for 5 seconds, during which HR was measured. On all psychometric measures, the PTSD+ subgroup was significantly different from the PTSD− subgroups (Combat + Noncombat), and the PTSD− subgroups did not significantly differ from each other. A linear deceleration in HR to CS+ and CS− signals was found in the combined PTSD− subgroup and on CS− trials in the PTSD+ subgroup, but was not present on CS+ trials in the PTSD+ subgroup. Results are interpreted with respect to a behavioral stages model of conditioned bradycardia and in terms of neural substrates which are both critical to HR conditioning and known to be abnormal in PTSD.
Article
The present study examined whether corneal air puff can be used as an unconditioned stimulus to elicit reliable classically conditioned heart rate (HR) responses in rabbits. The conditioned and unconditioned HR responses were assessed during Pavlovian conditioning with different intensities of paraorbital shock (2.7, 1.2, or 0.5 mA) or corneal air puff (18.3, 5.9, or 2.2 N/cm2) unconditioned stimuli (UCSs). Each experimental group was given one acquisition session during which an acoustic conditioned stimulus was paired with either the high, medium, or low intensity of a shock or air puff UCS. The results suggest that: a) HR is reliably conditioned with a high-intensity air puff UCS, and with medium- or high-intensity paraorbital shock stimuli; and b) only UCSs that elicit a tachycardiac unconditioned HR response reliably support HR conditioning. It was concluded that either air puff or paraorbital shock can serve as an effective UCS for HR conditioned responses.
Article
A review of the literature on aversive Pavlovian (classical) conditioning was conducted to de- termine whether various conditioned responses (CRs) develop at the same or at different rates. Statistical analyses revealed a bimodal distribution of the rates of acquisition of various types of CRs. Rapid acquisition (M = 5.7 trials to first consistent CR) occurs for conditioned suppres- sion and changes in galvanic skin response, blood pressure, respiration, pupil size, and heart rate. Slower acquisition (M= 71.3 trials) characterizes nictitating membrane, eyelid, and flexion CRs. Differences in conditioned stimulus intensity, unconditioned stimulus intensity, intertriaLinter- val, and interstimulus interval between the two groups cannot explain the dichotomy. Studies of concurrent measurement of more than one type of CR further support the "fast/slow" CR dis- tinction. The findings support two-factor theories of Pavlovian conditioning. The results are dis- cussed with regard to various two-factor learning theories, and the implications for behavioral and neurobiological studies of learning are considered. Since the pioneering work of Pavlov (1927), classical conditioning has been used in an enormous array of be- havioral and neurobiological studies. The fact that this research continues unabated is a testament to the power and richness of Pavlovian classical conditioning as a re- search tool. It also indicates that a satisfactory understand- ing of such learning is still sought. Many different behavioral response systems have been studied. A question that arises is, How "equal" are the various systems that have been recorded in Pavlovian con- ditioning? As an example, consider a hypothetical exper- iment in which simultaneous recordings are obtained from all possible response systems. Would conditioned re- sponses (CRs) appear in all systems at the same time? A number of theorists have suggested that the answer to this
Article
Comparisons of heart rate changes between experimental groups receiving paired presentations of tone (CS) and shock (US) and control groups that did not, indicated that conditioned responses occurred within 10 CS-US pairings, and were decelerative with latencies less than.5 sec. and durations of 8 sec. or more.
Article
In four classical conditioning experiments heart period and eyeblink responses were assessed concomitantly. The conditioned stimuli (CSs) were tones and the unconditioned stimulus (UCS) was a brief paraorbital electric shock. Using a 0.5-s duration CS, bradycardiac conditioned responses that consisted of a 4–5 ms change from pre-CS baseline occurred within 10–20 CS-UCS presentations. However, eyeblink conditioned responses began to occur only after 100–150 CS–UCS presentations. A 1.0-s CS duration resulted in bradycardiac conditioned responses of 15–30 ms change from pre-CS baseline, which again reached asymptote within 10–20 trials. Using a 4-s CS duration, in a differential classical conditioning paradigm, heart period discrimination between a reinforced CS+ and a nonreinforced CS− occurred within 10 trials; asymptotic performance of the heart period conditioned response occurred within 15 CS-UCS presentations and consisted of a bradycardiac response of 40–50 ms for the 12th interbeat interval following tone onset. These data thus indicate that these two model systems of mammalian learning (based on heart period and eyeblink responses) show quite different acquisition functions. It is also significant that heart rate slowing always accompanied the eyeblink conditioned responses, even though increases in general electromyographic activity as well as eyeblink conditioned responses were simultaneously observed during CS presentation.
Article
This study compares the time course of the cardiovascular changes (mean arterial blood pressure, heart rate) and behavioral changes (freezing, rearing, grooming and activity) evoked by 30 min long exposures to a footshock chamber before and after conditioning with footshocks. The main finding is that the conditioned fear evoked by re-exposure to the footshock chamber after conditioning is associated with a prolonged freezing response, a marked rise in mean arterial pressure (+35 mm Hg above a resting baseline of 105 mm Hg) and a delayed rise in heart rate. The pattern of behavioral and cardiovascular changes is the same as with conditioned fear to a discrete stimulus but the effect is a lot longer.
Article
Chronically instrumented, conscious rabbits were used to test the hypothesis that sensory stimulation with an air jet or oscillation produces differential hemodynamic changes that may be appropriate for an active or a passive behavioral response, respectively. Both stressors increased arterial pressure, central venous pressure, and hindquarters blood flow and produced visceral vasoconstriction. Neither stimulus altered hindquarters conductance. Although air jet increased heart rate and cardiac output, oscillation did not. The two stressors affected arterial baroreflex control of heart rate differently. Oscillation reset arterial pressure to a higher level with no change in heart rate maximum or minimum, whereas air jet reset both heart rate and arterial pressure to higher levels. Neither stressor affected baroreflex sensitivity. We conclude that the conscious rabbit shows at least two distinct cardiovascular responses when exposed to acute stressors. Air jet produces a cardiovascular response including tachycardia, which resembles the defense reaction and appears appropriate for active defense or flight. The response to oscillation, on the other hand, appears better suited for a passive response such as "freezing" behavior. During exposure to either stressor, the baroreflex is altered to allow simultaneous increases in heart rate and arterial blood pressure, but the sensitivity is maintained, allowing normal moment to moment control of heart rate.
Article
Examined the relative contributions of parasympathetic and sympathetic activity in controlling classically conditioned heart rate (HR) in 112 female Long-Evans rats in a 2 * 2 * 2 factorial design involving comparisons of the following factors: (a) conditioning vs sensitization, (b) vagal blockade vs nonblockade, and (c) acquisition vs extinction. Vagal blockade led to a substantial reduction in the performance level of the decelerative HR CR, but it did not appear to interfere with the learning of the CR as measured during extinction under saline. It is concluded that the magnitude of the CR was primarily mediated by increased vagal activity and that sympathetic involvement was minor. Results are related to a central state hypothesis which links together decelerative conditioned HR and inhibition of motor activity in the rat. (23 ref.)
Article
Extinction of Pavlovian fear conditioning in rats is a useful model for therapeutic interventions in humans with anxiety disorders. Recently, we found that delivering extinction trials soon (15 min) after fear conditioning yields a short-term suppression of fear, but little long-term extinction. Here, we explored the possible mechanisms underlying this deficit by assessing the suppression of fear to a CS immediately after extinction training (Experiment 1) and the context specificity of fear after both immediate and delayed extinction training (Experiment 2). We also examined the time course of the immediate extinction deficit (Experiment 3). Our results indicate that immediate extinction produces a short-lived and context-independent suppression of conditional freezing. Deficits in long-term extinction were apparent even when the extinction trials were given up to 6 h after conditioning. Moreover, this deficit was not due to different retention intervals that might have influenced the degree of spontaneous recovery after immediate and delayed extinction (Experiment 4). These results suggest that fear suppression under immediate extinction may be due to a short-term, context-independent habituation process, rather than extinction per se. Long-term extinction memory only develops when extinction training occurs at least six hours after conditioning.
Article
The effects of electrical stimulation of the posterior cerebellar vermis in anaesthetized, decerebrate and conscious animals are described, and include marked changes in blood pressure and heart rate and an inhibition of the baroreceptor reflex. These effects appear to be restricted to lobule IX, and can be duplicated by chemical stimulation, indicating that they are a genuine cerebellar phenomenon. The results of both neuroanatomical and neurophysiological experiments to investigate the pathways responsible for the effects are described, and these show there to be a direct projection of Purkinje cell axons to the parabrachial nucleus. Experiments designed to test a possible involvement of lobule IX in the alerting response have proved negative, and while lobule IX itself appears to have no role in conditioned cardiovascular responses, lesions of lobules VI and VII do result in a significant impairment of the acquisition of conditioned bradycardia in the rabbit.
Article
In the present study different heart rate patterns were demonstrated to accompany flight-fight behaviour, orienting behaviour and passive avoidance in rabbits. Flight-fight behaviour was characterized by markedly increased heart rate and diminished overall heart rate variability. The effect was mediated by vagal inhibition and beta-adrenergic activation in a type-specific relation. Orienting behaviour was accompanied by a smaller heart rate increase and the exaggeration of slow heart rate fluctuations. The latter effect was absent during beta-adrenergic blockade suggesting a behaviourally provoked beta-adrenergic activation. Single beta-adrenergic blockade did not change the characteristics of the heart rate fluctuations at rest. During passive avoidance a vagally mediated heart rate deceleration was followed by a slow heart rate return toward the initial heart rate level. This level was not reached during beta-adrenergic blockade. The enhanced overall heart rate variability during passive avoidance was mainly caused by strengthened respiratory-induced heart rate fluctuations and, furthermore, by exaggerated slow rhythmical heart rate fluctuations. The latter effect was not observed during beta-adrenergic blockade and is referred to as an orienting component within passive avoidance. Three individual behavioural types may be differentiated in rabbits 'Weisses Gross-Silber' by stable behavioural characteristics i.e. spontaneous motor activities, preferred postures at rest and coping behaviour. The results of the present study suggest that different neurovegetative reaction types, i.e. dominating beta-adrenergic or vagal activation are correlated with stable behavioural characteristics, especially in terms of preferring active or passive coping behaviour, respectively.
Article
Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions. These animals were compared on 4 sessions of Pavlovian eyeblink and heart rate conditioning, in which a tone was the conditioned stimulus and a paraorbital electrical shock was the unconditioned stimulus. Lesions of MD retarded acquisition of the eyeblink conditioned response and abolished the late-occurring tachycardiac component of the heart rate conditioned response. The data are compatible with previous experiments suggesting that MD participates in the sympathetic control associated with somatomotor learning.
Article
An acoustic stimulus previously paired with footshock elicits stereotyped increases in arterial pressure and heart rate and induces freezing behavior in freely behaving rats. Although the arterial pressure and freezing responses differ between groups given paired and random presentations of the tone and shock, the increases in heart rate do not. These observations, if taken at face value, suggest that the arterial pressure and freezing responses reflect associative learning but that the heart rate change is a nonassociative or a pseudoconditioned response. In this article we describe three experiments aimed at determining why the CS elicits similar increases in heart rate in groups given paired and random training. The first study demonstrates that regardless of the pseudoconditioning control procedure used (random, backwards, shock-alone, or naive), the same pattern of results is obtained: the increases in arterial pressure are greater in the paired than in each control group, but the heart rate rises to the same extent in all groups. The second study determined that the context in which the responses are tested (conditioning apparatus vs. novel test chamber) does not affect the general pattern of results obtained. The third study demonstrates that the superficially similar increases in heart rate in conditioned and pseudoconditioned rats are achieved by different physiological mechanisms: coactivation of the sympathetic and parasympathetic nervous systems in conditioned rats and sympathetic excitation alone in pseudoconditioned rats. Thus, the heart is influenced by associative emotional processes, but heart rate is not, under these conditions, a particularly useful index of those influences.
Article
Studied unconditioned heart rate (HR) response and conditioned HR and corneo-retinal potential (CRP) responses of a total of 75 naive New Zealand rabbits. 4 experiments were performed under conditions of cholinergic (muscarinic) and beta adrenergic and double blockades in which both adrenergic and cholinergic agents were combined. Results indicate that (a) the HR UCR was an acceleration, whereas the CR was a deceleration in rate; (b) both HR CRs and UCRs were decreased by the individual administration of adrenergic and cholinergic blockades and completely abolished by double blockades; (c) both blockades also decreased CRP conditioning, and the double blockade abolished CRP CRs; (d) although HR blockade by the peripheral cholinergic agent, methylatropine, and the centrally acting atropine sulfate were comparable, CRP CRs occurred after methylatropine administration but were almost completely abolished by atropine sulfate. (27 ref.)
Article
Examined the effects of alpha-adrenergic (hydergine) and cholinergic (flaxedil, atropine, bilateral vagotomy) blockades upon unconditioned (Exp. I) and conditioned (Exp. II) blood pressure (BP) and heart rate (HR) responses to tones and shocks. Ss were male albino rabbits (N =6 and 54, respectively) in both experiments. The relationship between BP increases and HR decreases, including response diminution to hydergine, suggests that BP increases contributed to HR decreases (CRs and UCRs). Additional observations, however, that HR UCRs were only partially related to BP responses, and that HR CRs occurred in the absence of conditioned BP responses, indicate that other mechanisms also influenced the HR decreases.
Article
Conducted an experiment with 72 male and female albino rabbits employing acquisition interstimulus intervals (isis) of 200 and 700 msec. And 3 subsequent isi shift conditions (fixed, gradual, and abrupt) with 2 directions of isi shift (short to long and long to short). The 200-msec isi resulted in fewer trials to the 1st cr and a higher overall level of percentage crs. The percentage crs under the short-to-long isi shift fell significantly below the long-to-short and fixed isi conditions. Cr onset latency, cr peak latency, and cr topography altered in the direction of isi shift. It is concluded that the instrumental response-shaping hypothesis cannot presently account for major portions of the percentage cr data. (18 ref.)
Article
ASSESSED DIFFERENCES IN ACQUISITION AND DISCRIMINATION AMONG NICTITATING MEMBRANE (NM), HEART RATE (HR), AND RESPIRATION RATE (RR) RESPONSE SYSTEMS IN A CLASSICAL CONDITIONING EXPERIMENT. 4 GROUPS OF 8 RABBITS WERE GIVEN ACQUISITION AND EXTINCTION TRAINING IN A DESIGN THAT REINFORCED EITHER 1 OR 2 OF 3 TONES IN EITHER A UNIDIRECTIONAL OR A BIDIRECTIONAL MANNER. FASTEST RATES OF CR ACQUISITION AND DISCRIMINATION FORMATION AS WELL AS GREATEST DISCRIMINATION CAPABILITY WERE REVEALED IN THE HR SYSTEM. THE RAPID ACQUISITION OF HR DISCRIMINATIONS RELATIVE TO SLOWER ACQUISITION AND DISCRIMINATION FORMATIONS OF NM RESPONSES INDICATED THAT NM ACQUISITION CURVES REFLECT SOMETHING IN ADDITION TO AN S'S LEARNING THAT A UCS FOLLOWS A PARTICULAR CS.
Article
The present experiments were undertaken to assess the relative contributions of the vagi and cardiac sympathetics to conditioned heart rate changes in the pigeon. The cardiac response was established using a defensive conditioning paradigm in which light was paired with foot-shock. Birds with bilateral cervical vagotomy, beta-blockade (propranolol), or both were studied in this situation and their conditioning performances compared with those of control animals.Conditioned cardioacceleration in vagotomized birds was significantly below that of control animals, although substantial conditioning still occurred. However, following beta-blockade conditioned rate responses were markedly reduced, almost no conditioned cardioacceleration appearing until late in training. Bilateral vagotomy prolonged the latency of the response, while a short latency heart rate change could still occur following beta-blockade. Functional denervation with combined vagotomy and beta-blockade prevented the conditioned response completely.Successful differentiation performance was obtained in birds with either vagotomy or beta-blockade, but vagotomized animals required longer training to establish such differential responding.These results suggest the following conclusions: (a) Conditioned cardiocceleration is mediated entirely by the extrinsic cardiac nerves. (b) The principal contribution to the magnitude of the response is mediated by the cardiac sympathetic nerves. (c) The shortest latency component of the response in mediated by the vagi. (d) Either nerve supply is capable of mediating differentiation, but it is more difficult to establish with only excitatory innervation of the heart.
Article
Investigated the problem of differentiating orienting reflexes (ORs) from defensive reflexes (DRs). 120 male college students were employed in a factorial design which manipulated stimulus intensity, duration, and interstimulus interval. The Ss received 30 presentations of white noise with a particular combination of stimulus parameters. Recordings were made of forehead blood content (BC), heart rate (HR), skin potential (SP), and skin conductance (SC). Forehead BC did not differentiate between ORs and DRs; however, HR and SP showed differences in magnitude and form of response and rates of habituation as a function of stimulus intensity. The physiological data are related to Ss' verbalizations about the loudness and unpleasantness of stimuli, and interpretations about the autonomic indexes of ORs and DRs are offered.
Article
Curarized and subjected 12 normal and cardiac sympathectomized dogs to either signaled or unsignaled shocks. The unsignaled shocks were of several intensities and durations. There were no differences between signaled and unsignaled shocks in their effects on heart-rate, systolic, and diastolic blood-pressure responses. Following the termination of shocks shorter than 5 sec., and during shocks longer than 5 sec., heart rate decreased while blood-pressure indices increased. Heart rate fell below base-line levels directly after stimulus termination although blood-pressure indices were still elevated. This deceleratory overshoot increased over trials of signaled shock in all sympathectomized Ss. Such functional differences between heart rate and blood pressure preclude the strong inference that heart rate is a direct measure of sympathetic activation. (29 ref.)
Article
The effects of 4 CS-UCS conditions upon physiological responses were studied. The conditions were forward and backward conditioning, UCS alone, and unpaired CS and UCS. 6 test, 42 "conditioning," and 4 extinction trials were given. Analysis of variance was used for 3 measures of electrodermal response (EDR) and 4 measures of heart rate. Significant group differences for EDR amplitude were found on test and extinction trials. The UCS-alone and forward-conditioning groups had higher amplitudes during conditioning. During extinction the forward-conditioning group continued to exhibit higher amplitude. The findings for 3 conditions were accounted for by orienting-response theory, but those for forward conditioning were not.
Article
The dimensions of a 2 × 2 factorial design with 8 Ss per cell were injection of Flaxedil or saline, and paired or unpaired presentations of a tone CS and shock US. Rabbits, either immobilized by Flaxedil or run in the normal state, revealed reliable conditioning of heart-rate deceleration, blood pressure elevation, and neocortical desynchronization. The results suggested that the classically conditioned heart-rate deceleration is essentially autonomic, and that this heart-rate deceleration reflects a compensatory response to a sympathetically induced elevation in blood pressure.
Article
The present experiments examined the effects of peripheral administration of atropine methyl nitrate and 6-hydroxydopamine hydrobromide on differential classical conditioning or eye-blink (EB) and heart rate (HR) responses in the rabbit. Atropine decreased HR conditioned response (CR) magnitude and increased baseline HR, although the latter declined somewhat over the first few sessions of the experiment. As baseline HR declined, EB CRs increased in animals treated with atropine. However, the acquisition of the EB response was impaired in these subjects compared with animals treated with saline. The administration of 6-hydroxydopamine produced an impairment of the HR response early and late during acquisition but had no effect on EB conditioning. Control experiments suggested that the impairments produced by methyl atropine were not due to general somatomotor deficits or to a differential sensitivity to the electric shock unconditioned stimulus. The conditioning data are consistent with the Laceys' peripheral afferent feedback hypothesis of autonomic-somatic relations.
Article
We examined the role of the cerebellum in classical conditioning of the nictitating membrane response (NMR) of rabbits by comparing the effects of unilateral and bilateral cerebellar cortical lesions. Using extended preoperative conditioning to ensure high levels of learning, we confirmed that unilateral lesions of lobules HVI and ansiform lobe impaired conditioned responses (CRs) previously established to an auditory conditioned stimulus, but did not prevent some relearning with post-operative retraining. Bilateral lesions of HVI and ansiform lobe produced similar impairments of CRs, but also prevented subsequent relearning. Unilateral cortical lesions produced significant enhancement of unconditioned response (UR) amplitudes to periorbital electrical stimulation. Bilateral cortical lesions enhanced UR amplitudes to a lesser extent. Because there was no correlation between the degree of CR impairment and UR enhancement across the unilateral and bilateral lesion groups, the suggestion that the lesions impaired CRs due to general effects upon performance, rather than due to losses of learning, is not supported. Both sides of the cerebellar cortex contribute towards learning a unilaterally trained CR. This finding is important for the re-interpretation of unilateral, reversible inactivation studies that have found no involvement of the cerebellar deep nuclei in the acquisition of NMR conditioning. In addition, we found conditioning-dependent modifications of unconditioned responses that were particularly apparent at low intensities of periorbital electrical stimulation. This finding is important for the re-interpretation of studies that have found apparent changes in the UR of conditioned subjects after cerebellar lesions.
Article
Robust classical conditioning modifies responding to the unconditioned stimulus (US) in the absence of the conditioned stimulus (CS), a phenomenon the researchers called conditioning-specific reflex modification. Unconditioned responses (URs) to periorbital stimulation varying in intensity and duration were assessed before and after 1, 3, or 6 days of paired, explicitly unpaired, or no presentations of tone and electrical stimulation. After 3 days of pairings, conditioned responding (CRs) reached 94%, and there was an increase in latency to the peak of URs. The peak latency increase was replicated in a second experiment where rabbits reached asymptotic conditioning during 6 days of pairings. There was also a conditioning-specific increase in the amplitude of URs. There were no UR changes as a function of low level of CRs following 1 day of pairings. Data suggest that there are learning-specific changes in pathways mediating the US/UR, as well as in those mediating the CS/CR.
The ECG is routinely used in many species to monitor effects of drugs. While it is relatively easy to measure both PR and QRS, measurement of QT is complicated by the fact that this interval can change with heart rate. In order to compensate for variations in QT due to variations in heart rate, various correction factors have been used, including those of Bazett and Hodges. Such corrections were devised for humans and may have limited applicability in other species. We have systematically varied heart rate in anesthetized rats, guinea pigs, rabbits, and primates using procedures such as vagal stimulation, direct atrial stimulation, injection of cold saline and drugs, including anesthetics, and measured the resulting QT (as QaT and related measures). Over a wide range of heart rates we tested various formulas for their value in correcting for the variation in QT interval associated with changes in heart rate. In rats the "QT" interval did not change appreciably with heart rate. In the other species QaT intervals varied in the expected manner with heart rate in that they decreased with tachycardia and increased with bradycardia. Various formulas were tested for their utility in correcting measures of the QaT interval (QaTc) for changes in heart rate in guinea pigs, rabbits, and primates. In species other than rats, there was little difference between the various formulas in their ability to increase the precision of QaTc and the normality of its distribution, although the best correction is that derived from the regression (either linear, square root, or polynomial) equation relating RR and QaT.
Article
Electrical stimulation of area 24 and area 32 of the medial prefrontal cortex (mPFC) in rabbits elicited increases in respiration rate and decreases in heart rate (HR) and blood pressure. However, stimulation in area 25 elicited pressor responses and a biphasic HR response consisting of an initial HR increase followed by an HR decrease. Administration of an alpha-adrenergic receptor antagonist eliminated the pressor response and bradycardiac response produced by area 25 stimulation but it had no effect on the bradycardia elicited by stimulation of area 24 or area 32. Lesions centered on area 32 of the mPFC greatly attenuated the conditioned bradycardiac response elicited by paired tone and paraorbital shock presentations. Lesions of area 24 produced a decrease in discrimination between a reinforced conditioned stimulus and a nonreinforced conditioned stimulus but had no effect on the magnitude of the conditioned response. Area 25 lesions had no effect on any aspect of conditioned responding.
Article
The present study was conducted to test the hypothesis that the paraventricular nucleus of the hypothalamus (PVN) is involved in the mediation or modulation of the cardiorespiratory components of the defense reaction (DR) in rabbits. Electrical stimulation of the PVN elicited increases in blood pressure and heart rate, hyperventilation, decreased blood flow to the visceral organs, and an increase in blood flow to the hindlimbs that was mediated by an atropine-sensitive vasodilation system. This response pattern is nearly identical to the one that is elicited by electrical stimulation of the hypothalamic defense area. In addition, the cardiomotor component of the baroreceptor reflex was observed to be suppressed during electrical stimulation of the PVN. Previous studies have shown that electrical stimulation of the hypothalamic defense area also leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of the present study provide evidence that the PVN is involved in the mediation or modulation of the defense reaction.
Article
Benzodiazepine receptor (BZR) agonists are prototypic anxiolytic agents, whereas BZR inverse agonists exert anxiogenic effects. The effects of these compounds offer a potentially important pharmacological model system to examine the central mechanisms of anxiety. In accord with its putative anxiogenic properties, we previously found that the BZR partial inverse agonist, FG 7142, enhances the cardiovascular defensive response to a nonsignal acoustic stimulus in rats. In contrast, we found in the present study that this agent attenuates both the somatic and cardiovascular components of the acoustic startle response. BZR agonists and inverse agonists are known to modulate the basal forebrain cortical cholinergic system, and we consider the potential involvement of this system in the disparate psychophysiological actions of FG 7142 and in anxiety states in general.
Article
The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.
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Rabbits with lesions of either medial prefrontal cortex (mPFC) or amygdala central nucleus (ACN) were compared with sham-lesioned animals during differential and reversal classical conditioning of the eyeblink (EB) and heart rate (HR) response. Lesions of the mPFC, but not ACN, produced a severe impairment in EB reversal conditioning, but neither lesion affected original discrimination. However, both mPFC and ACN lesions produced a severe attenuation of accompanying HR decelerations during both initial differentiation and reversal. These results suggest that mPFC processing of Pavlovian conditioning contingencies affects not only the autonomic component of learning but preservative somatomotor conditioning as well, whereas ACN processing affects only the autonomic component.
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There has been a renewed interest in the neural basis of fear conditioning to context. These current approaches are accompanied by some limitations including the use of short testing windows, non-discriminative paradigms, and unitary fear response assessment. In an attempt to circumvent these limitations, a discriminative context procedure assessing multiple response measures of fear was used in the present study. Conditioning consisted of three training sessions and each session consisted of 2 days. On day one, the animals were placed in the paired context and received three foot shocks. On the other day, they were placed in the unpaired chamber in the absence of any aversive event. Animals were tested after each training session and the response measures of fear recorded included: preference, freezing, heart rate, ultrasonic vocalizations, defecation, body temperature, urination and locomotion. The results suggest that behavioral, as well as physiological changes evoked by fearful stimuli become associated with the context in which the aversive event occurred. In general these findings also suggest that there are different learning parameters for the measures of fear examined in this paradigm.
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The effects on the expression of conditioned bradycardia of pairing an early (fourth postnatal day) cerebellar vermal lesion with a lesion of the medial prefrontal cortex (mPFC) were studied in adult New Zealand rabbits. In the conditioning procedure, an auditory stimulus (5 s, 1000 Hz) served as a conditioning stimulus (CS) and a train of electrical impulses applied to the ear (500 ms, 100 Hz, 1.5 mA) was used as the unconditioned stimulus (US). Heart rate (HR) responses exhibited by rabbits with the early double lesion (PFCBs) during orientation (CS-alone) and conditioning (CS-US paired) were analyzed and compared with those shown by unoperated controls as well as by a group of animals in which a cerebellar lesion alone had been performed on the fourth postnatal day (CBs). In all the experimental groups vermal lesions were localized in the cortex of lobules V-VII and the underlying white matter. As for mPFC ablation, the lesioned area involved the agranular precentral region (Brodmann's area 8), the anterior cingulate cortex (Brodmann's area 24) and the prelimbic area (Brodmann's area 32). All the experimental animals had a normal baseline HR as well as a marked orientation response, both comparable with those exhibited by controls. In contrast, while CB rabbits showed an increase in the amplitude of the conditioned bradycardic response when compared with controls, the HR conditioned response of PFCB animals was comparable to that exhibited by controls. These results suggest that, since the double lesion produces a conditioned bradycardia similar to that of the controls, the increase in the amplitude of this response observed after early cerebellar removal may depend on the mPFC which, in the absence of specific cerebellar circuits, is unable to produce a properly calibrated HR conditioned response.